In a recent study published in Scientific reportsThe researchers conducted a systematic review and meta-analysis to find out if influenza vaccination can reduce the severity of the effects of coronavirus disease 2019 (COVID-19).
Studies have reported potential mechanisms for the protective efficacy of influenza vaccination against the severity of SARS-CoV-2 infection, including (i) the presence of an MF59 adjuvant in influenza vaccines, which enhances the immune response against SARS-CoV, and (ii) influenza vaccines. may stimulate innate immunological memory cells designed to mount an immune response against other respiratory pathogens such as severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) and (iii) influenza A virus and SARS-CoV-2 interacting with tetraspanin antibodies and angiotensin-converting enzyme 2 (ACE2). However, the results of potential protection against the severity of COVID-19 by influenza vaccines have been inconsistent.
About the study
In this systematic review and meta-analysis, investigators assessed the association between influenza vaccination and COVID-19 severity.
Databases such as PubMed, Embase, Scopus, OVID, Cochrane Central, and Web of Science were searched through August 5, 2021. In addition, the team manually searched Google Scholar for relevant studies and links to included studies. The analysis was performed in accordance with the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) and PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines.
Studies were included if (i) they were observational prospective or retrospective studies (cohort and case-control), (ii) were conducted in patients with COVID-19, and (iii) compared patients who tested positive for SARS-CoV-2 who were given influenza vaccines and SARS-CoV-2-positive patients did not receive influenza vaccines.
Studies were excluded if (i) no health-related outcomes were reported, (ii) influenza vaccination was not an impact, (iii) patients without a confirmed diagnosis of COVID-19 were included, (iv) studies of environmental type (v) data were not available authentic or duplicated, (vi) research published in languages other than English, (vii) conference abstracts, book chapters, editorials, letters, commentaries, and animal studies.
The included studies were independently reviewed by two reviewers, data were extracted by four reviewers, and disagreements were resolved by an additional reviewer. Data were obtained on a summary of eligible studies, study design, country, number of COVID-19 patients vaccinated against influenza, year of vaccination, and SARS-CoV-2 testing reports. Patient data on demographics, comorbidities, outcomes such as mortality rates, hospitalizations, intensive care unit (ICU) admissions, length of stay, length of stay in intensive care unit, ventilator requirements, COVID-19 associated pneumonia and frequency of symptoms.
The quality of the included studies was assessed using the Newcastle-Ottawa (NOS) score, and subgroup analyzes were performed for mortality rates by geographical stratification of patients living in Italy, the United States of America (USA), and other countries. Dichotomous and continuous data were obtained and pooled as hazard ratio (RR) and mean difference (MD), respectively. Fixed effects and random effects models were used for homogeneous and heterogeneous data, respectively.
A total of 6058 records were identified and 450 records from databases and other data sources, respectively, of which only 23 full-text articles were assessed for eligibility after removal of duplicate records (n=4690), studies conducted for SARS-CoV -2-negative patients (n=4), repeat studies (n=1), comments (n=1) or letters to the editor (n=1). As a result, 16 and 13 studies were included in a qualitative analysis (systematic review) and a quantitative analysis (meta-analysis), respectively.
The review included cohort studies (n = 14) and case-control studies (n = 2) including 244,642 people, of which 191,496 people were positive for SARS-CoV-2. The studies were conducted in Italy (n=6), USA (n=5), Poland, Brazil, Iran, England and Spain. Based on the NOS scale, nine studies (out of 16) received full scores, while the remaining seven studies received eight points (out of nine), and all included studies had a low risk of bias.
In terms of mechanical ventilation requirements, the results of the analysis significantly favored patients who received influenza vaccines compared to those who did not receive influenza vaccines (RR = 0.7). However, no significant differences were observed between vaccinated and unvaccinated patients in mortality (RR = 1.2), hospitalizations (RR = 1.0), and intensive care unit (ICU) admissions (RR = 0.8). After subgroup analysis, the results were not significant for individuals living in the US (RR=0.8), Italy (RR=1.9) and other countries (RR=1.0).
Overall, the results of the study significantly favor mechanical ventilation for influenza vaccinated SARS-CoV-2 patients who received influenza vaccines compared to unvaccinated SARS-CoV-2 positive patients. However, there were no statistically significant differences between influenza vaccinated and unvaccinated SARS-CoV-2-positive patients in terms of mortality, hospitalization, duration of hospitalization, ICU hospitalization, ICU duration, and development of COVID-19 symptoms.
However, the study has several limitations such as (i) inclusion of a retrospective type of study, (ii) data heterogeneity, and (iii) viral infections other than COVID-19 were not evaluated in most of the included studies. . During the COVID-19 pandemic, the importance of influenza vaccination cannot be underestimated. Further research, including high-quality RCTs (randomized controlled trials), is needed to further investigate the effectiveness of regularly updated influenza vaccines in relation to COVID-19 severity. Potential confounding factors such as socioeconomic status and health literacy also need to be considered.